Professional Documents
Culture Documents
Manuf Lec Finals PDF
Manuf Lec Finals PDF
A. AQUEOUS SOLUTIONS
1. Aromatic water - clear saturated aqueous solution of volatile oils
or other aromatic substances.
- flavorant, perfumed vehicle, aqueous phase in
emulsion & suspension/
-solution method - 2mg in 1L of water.
-alternate solution method: triturate, dispensing
agent(TALC) 2mg/mL - dissolve in 1mL water.
DISADV: deteriorate with time, decreases solubility of different
substances, air tight - light-resistant container - small quantity.
ETHEREAL SOLUTIONS
1. Colloidons - applied to skin, leave film
- containing, pyroxylin in mixture of 3 parts ether
(ethyl/ester) & 1 part alcohol (ethanol)
Pyroxylin - soluble gum cotton, colloidal cotton, nitrocellulose
- mix of nitric and sulfuric acid on cotton
Flexible colloidon - 2% camphor (water proof)
-3% castor oil (flexibility)
-water repellant protective,protecting for minor
cuts, chigger bites
Reduce or eliminates the side effects of fluorocacil treatment.
-reduce or eliminates stinging of the skin
- not for solar ketosis
Salicylic acid colloidon - flexible colloidon + 10% SA
- for warts with less irritation
VAPORIZATION
1. Inhalation - administered through nasal route and oral respiratory
route, gives local/systemic effect
-aerosols & innert gas ; vapor or mist
- relief from bronchial & nasal congestion
Ex. Nebulizers (inert gas) &
metered dose inhaler (propellant)
Decongestant = sterile water(nebulizer) and Na Cl
Metered dose=
Epinephrine = intermittent asthma
Isoproterenol = bronchoconstriction
Phenylephrine = decongestant
Size of API = 0.5 -7 micrometer( to penetrate properly to
pulmonary arteries)
TOPICAL SOLUTIONS
1. Sprays = either aqueous or oleaginous
= coarse droplets or finely divided powders
= nasopharyngeal tract or skin
2. Astringents = constricts pores & precipitate skin
Ex. Aluminum Acetate, Aluminum subAcetatte, Calcium
Hydorxide soln
1. Extracts:
3 forms:
Semi-liquid =hydrophobic & more non polar
constituents.
=syrupy consistency
Pillular/solid = plastic consistency
=ointment & suppositories & pills
Ex. Pure glycerin, usp
Powders = tablets and capsules
-Belladona extract
DISPERSED SYSTEM
A. SUSPENSIONS
*cake = agglomeration
Hammer milling = grinding with impact forcing them out on screen.
-screen (4-325)
- produce particle size: 10-50 micrometer
Fluid energy grinding = particle size: below 25 micrometer
- violent turbulence in high viscosity air.
- impaction & friction
Ball milling: ceramic balls rotating in a drum
- 20 - 200 mesh
- attrition & impact
Roller milling: 2 or more rollers revolves at different speed.
- 20 - 200 mesh
- compression & shearing
Formulation
1. API: minimum degree of solubility
2. Dispersing medium: non toxic, can be non aqueous or
aqueous
3. Wetting agent: displaces air or release trapped air
4. Suspending agent: controls Sedimentation rate
EMULSION
= 2 immiscible liquids; 1 is dispersed uniformly through out other.
Dispersed phase(internal/continuous phase): -dispersed in
small droplets.
Dispersion medium(external/discontinuous phase): -external
or discontinued
-more amounts
Emulsifying agent: - uniformly dispersed medium in phase
- stability
Ex. W(phase)/O(medium)- more occlusive and emollient
O/W: removed easily with water
Formulation:
1. Internal
2. External
3. Emulsifier
4. Antioxidant
5. Humectant - preserve moisture
6. Preservative, colorants
COLLOIDAL DISPERSION/SOL
1. Aerosols - Colloidal systems consistency of very finely divided liquid or
solid dispersed in and surrounded by a gas (mist, foam, or
semisolid)
Types:
Space sprays (<50micrometer)
Surface sprays ( 50-200 micrometer)
A. POWDERS – intimate mixtures of dry finely divided drugs or chemical that are intended for internal
external use.
- Also used as pharmaceutical dosage form
- ADV: flexibility in compounding
- DISADV: easily wetted by liquids, inaccurate dose, prone to hygroscopicity
Comminution of drugs:
Particle size:
- Trituration or comminution – using mortar and pestle; used in small scale manufacturing,
extemporaneous compounding
- Milling – used in large scale production
- Levigation – used to provide smooth paste; using levigating agent (mineral oil, glycerin or
propylene glycol) + with powder in mortar and pestle
- Pulverization with intervention – adding a volatile solvent to a substance/powder compounds
ex: camphor + alcohol or iodine crystals + ether
Blending:
1. Volatile substances
Examples: • Camphor, Menthol and Essential oils
– to prevent the volatilization when mix with powders, it should be stored in a heat-sealed plastic
bag or double wrapped with a wax or glassine paper inside a bond paper
2. Eutectic mixtures – mixtures of two or more components which usually do not interact to
form a new chemical compound but inhibits the crystallization process of one another which
results to low melting point than the other compound, therefore add inert diluent to prevent
eutecsia.
Examples: • Phenol, Camphor, Menthol, Thymol, Antipyrine, Phenacetin, Acetanilide,
Aspirin, Salol
Effective diluent: Light magnesium oxide and magnesium carbonate (Preferable)
We can also use Kaolin, starch and bentonite
• In adding, add the same amount of diluent and eutectic compounds to prevent the
liquefaction for two weeks
• Two ways in mixing:
- Each eutectic compound should be mixed first with a portion of the diluent and gently
blended together, preferably with a spatula on a sheet of paper; used equal amount of
diluent
- Deliberate forcing of the formation of the liquid state, by direct trituration, followed by the
absorption of the moist mass; require huge more amount of diluent than eutectic mixtures,
therefore occurs more advantage of extended product stability; useful for dispensing large
number of doses that are normally would not be consume for a period of 1 to 2 weeks.
• For Aspirin and phenyl salicylate – add silicic acid (20%, PS: 50mm) to prevent
eutecsia
TYPES OF POWDERS
Bulk powders
A. Oral powders
i. Finely divided powders – Intended to be suspended or dissolve with water or mix with food.
• Antacid
• Laxative powders
ii. Effervescent granules – Sodium bicarbonate and citric acid/tartaric acid/sodium
biphosphate in addition active ingredient
• mix with water, it releases CO2 because of the acid-base reax
• serves to mask the salty and bitter taste of medication
B. Dentifrices
- Contains a soap or detergent, mild abrasive and an anticariogenic agent (Prevents tooth decay;
used for cleaning and polishing of teeth; usually contains fluoride)
C. Douche powders – used for antiseptic/cleansing agents for body cavity; commonly for vaginal use;
also used as nasal, ophthalmic, otic; completely soluble which is intended to be dissolve in water prior
to use
- Powders contains aromatic oils preparations should passed through sieve no. 40 and 60 (to
prevent agglomeration and ensure complete mixing); then store in bulk powder boxes,
however preferable with glass containers (protect them against loss of volatile materials and
easy access for patients)
D. Dusting powders – locally applied non-toxic preparations that are intended to have no systemic
action; dispense in a sifter-top packages or a pressure aerosols (more preferable; ADV: it has the
ability to protect the product from moisture, air and contamination and convenient for application.
DISADV: more expensive)
- Applied as lubricants, protectives, absorbents, antiseptics, antipruritics, antibromhidrosis
agents (used with condition of abnormal/offensive body odor caused by too much secretion
of apocrine gland), astringent, and antiperspirants
- Powders are passed thru sieve no. 80 or 100
- Example: baby powder, foot powders
- Take note of the ingredients used: ex: Boric acid – when absorbed in large areas of abraded
skin can caused toxic reaction in infant
Zinc stearate powders – accidental inhalation can lead to pulmonary inflammation of lungs in
infants
E. Insufflations – Finely divided powders that are introduced/designed to be blown into the body
cavities e.g. ears, nose, throat, tooth socket, and vagina using the device insufflator
- Difference with dusting powders is the device used
- DISADV: in using insufflator: there is a difficulty in obtaining uniform dose that has
restricted their general used; therefore specialized equipment is used called:
• Aerohaler (thru inhalation the px causes a small ball inside the device to strike a cartridge
containing the drug; provides a proper amount of powder) and
• Spinhaler turbo-inhaler (a propeller-driven device that is designed to deposit a mixture of
lactose and micronized cromolyn sodium into the lungs as an aid in the management of bronchial
asthma)
- Pressure aerosols – used to administer potent drugs; this method overs the advantage of
excellent control of dose thru metered valves as well as product protection.
F. Triturations – dilution of potent powdered drugs that are prepared by intimately mixing them with a
suitable diluent in a definite proportion by weight; for extemporaneous compound of potent drug
Procedures:
1. Reduce the rug to a moderately fine powder in a mortar and pestle
2. Add about an equal amount of diluent and mix well by thorough trituration in mortar
3. Successively add portions of diluent, triturating after each addition, until entire quantity of diluent
has been incorporated
B. CAPSULES – medicinal agents or inert substances are
enclosed in small shell of gelatin
ADV: renders the compound tasteless; easy to administer and
to filled an extemporaneously or large quantities commercially;
and permits flexibility in an exact dosage level
DISADV: cannot used for administration of extremely soluble
materials e.g. potassium chloride, potassium bromide,
ammonium chloride; cannot used also in highly efflorescent
(loses water due to hydrated salt) and deliquescent materials
Types:
Both are made up of Gelatin that is prepared by enzymatic hydrolysis of collagen; collagen is the main
protein constituents of the connective tissues of animal, bones and skin.
• Gelatin A – Acid hydrolysis of porcine skin
• Gelatin B – Base hydrolysis of bovine bone
1. Hard Gelatin Capsules – Aka. Tri-filled capsule; made of gelatin + sugar + water; it may also
contain colorant and an opacifying agent; consist of two section: Cap (smaller size); Body (longer
size);
- Added with 0.15% sulfur dioxide – to prevent decomposition during manufacturing
- 12% - 16% moisture
Process made in incorporating of powders to capsules:
• Punch method
• Hand-operated filling machine
2. Soft gelatin capsule – globular-shaped; gelatin shell is thicker than hard gelatin; made of gelatin
+ glycerin or polyhydric alcohol (sorbitol); glycerin & sorbitol renders the elasticity and plasticity of
soft gelatin capsule; contains preservatives to prevent the growth of fungi
- 6% - 10% moisture
- Used for:
• water-immiscible volatile and non-volatile liquids
• water-miscible non-volatile liquids
• water-miscible and relatively non-volatile compounds
Process:
• Plate process
• Rotary die process
• Reciprocating die process
• Aquogel capsule machine – used to incorporate dry powders thru soft gels
C. TABLETS – mixture of active substances and excipients usually in powder form and compacted into
solid; contains with or without diluent which is prepared either by compression or molding methods
Types:
1. Compressed tablets – made by wet granulation or dry granulation or direct compression; made
from powdered crystalline or granular materials alone or with combination with binders,
disintegrants, controlled-release polymers, lubricants, diluents and colorants; more available in the
market; either coated or uncoated
a. Sugar coated – coated with sugar to improve the palatability of the preparation; sugar
contains at least 50% of the tablet bulk
b. Chewable tablets – intended to be broken or chewed before ingestion; contains mannitol
which adds the 50% of the tablet bulk; to make it sugar-free add xylitol.
c. Film coated – coated with thin layer of polymer capable of forming skin-liked film; less bulky
d. Enteric-coated – coated that it will disintegrate in the intestinal fluid; has delayed-release
mechanism
e. Multiple compressed – compressing the film material more than once, it can be:
• layered - prepared by compressing additional tablet granulation on the previously compressed
granulation, it is repeated to give a multi-layered tablets of at least 2 to 3 layers
• pressed coated or dry coated – tablet within the tablet; prepared by feeding previously
compressed tablets into a special tableting machine and then compressing another granulation
layer around the pre-formed tablet. ADV: separate incompatible drug substances and provide
enteric coating to the core tablet.
f. Controlled-release tablets AKA. Prolonged release or sustained-release - releases the
medication over a period of time
g. Tablets for solution – intended to be dissolve in a solution; used for preparing solution or in
imparting giving characteristic to solution; labeled as not to be swallowed. Example: • Halazone
tablets, Potassium permanganate tablets
h. Effervescent tablets – intended to be dissolve in a liquid; compressed granular effervescent
salt that contains sodium carbonate, citric acid and tartaric acid; liberates CO2 that acts as
disintegrator; labeled as not to be swallowed
i. Buccal (dissolves in the buccal or cheeks) & Sublingual (dissolves under the tongue) –
formulated and compressed with sufficient pressure to give a hard tablet; some sublingual are
formulated to melt at body temperature, it gives rapid absorption, and use in purely soluble
compounds
j. Immediate release - designed to release their medications with no rate controlling features
k. Modified release – has drug release features based on time, course or location
Types:
• Extended release AKA. Controlled release – release medication over an extended period
• Delayed release – Releases medication at a time other than promptly after administration
• Repeat action – two single doses, one for immediate action and other is delayed release
• Targeted release – directed towards a region, a tissue or site of absorption.
2. Molded tablets/Tablet triturates – made from moist materials using triturate mold that gives
them a shape of cat section of a cylinder; used for potent drugs and tablets must be completely
and rapidly soluble.
Problem: During compression, it is very difficult to find a lubricant that is completely water-
soluble.
a. Dispensing tablets AKA. Compounding tablets – provides a convenient quantity of potent
drug that can be incorporated readily into powders and liquids; supplied primarily as
convenience for extemporaneous compounding and never dispense as dosage form
b. Hypodermic tablets – soft readily soluble tablets; originally used for preparation of solutions
to be injected; no longer use today because of the difficulty in achieving sterility and most
parenteral solutions are available for most drug substances
c. Vaginal tablets AKA. Vaginal inserts – bullet or ovoid-shaped that is inserted in the vaginal
for local or systemic effect
---------------------------------------------------------------------------------------------------------------------------------------
B. MIXING
1. Tumbling mixers or blenders – commonly used for granules and free flowing powders;
generally mounted so they can be rotated about an axis
2. High-speed mixer-granulators – both mix and granulate a product
3. Fluidized-bed mixers – mainly used for dry granules and coating multi particles; mixing, drying,
and coating
4. Agitator mixers – depend on the motion of the blade or paddle through the product; mechanism:
convective mixing (inversion of the powder bed using a blade or a paddle in which large mass of
materials moves to one place to another)
DISADV: dead spots may not be eliminated during process; substances may not be mix properly
C. GRANULATION
Methods:
1. WET GRANULATION – process in which powder particles are made to adhere to form a larger
multi particle entities called granules
Size produced: 0.2mm – 4mm | Tablets & capsules: 0.2 – 0.5mm
- Oldest and widely used method involved wet massing and the wet mass is force in a sieve
to produce a granules and then dried
- Involves the massing of a mix of dry powders particles using a granulating fluid
- ADVANTAGES:
• Improved cohesiveness and compressibility of powders with formulation of granules
• Suitable for high dosage drugs with poor flow or compressibility
• Good distribution and uniform content for soluble low-dosage drugs
• Good color distribution
• Ensures fixed composition of each granule during processing, transport and handling
• Improved dissolution rate of hydrophobic
- DISADVANTAGES:
• Very costly because of several steps to imploy
• time and labor consuming
• not useful for water and heat sensitive drugs
- General steps:
1. Milling of raw materials
2. Weighing of raw materials
3. Dry mixing of milled raw materials: active, diluent internal disintegrant
4. Wet mixing: incorporation of binder solution
5. Granulation and screening of the damp mass using 6-12 mesh screen
6. Drying
7. Dry screening through smaller mesh screen (no. 14-20)
8. Final mixing: addition of lubricant and external disintegrant
9. Compression
2. DRY GRANULATION - primary powder particles are aggregated under a high pressure; done
through
• slugging - includes a heavy duty tablet press that usually produces large tablets
• roller compaction - powder is being squeeze between two rollers to produce a sheet of
materials.
- ADVANTAGES:
• Use for drugs that do not compressed well after wet granulation
• Materials that are sensitive to moisture
- DISADVANTAGES:
• Does not permit uniform color distribution
• Tendency to create more dust
• Must have an inherent binding properties
- Example of drugs:
• Thiamine HCl
• Aspirin
• Ascorbic acid
• Magnesium Hydroxide
- General steps:
1. Milling
2. Weighing
3. Mixing: active, diluent, and a portion of lubricant
4. Slugging or precompression
5. Granulation and sieving
6. Final mixing: Lubricant & Disintegrant
7. Compression
3. DIRECT COMPRESSION – not part of granulation; it is the method used in compressing the
tablets
- Preferred method in manufacturing the tablet; tablets are compressed directly from powder
blends of actives and suitable ingredients
- Uses directly compressible vehicle e.g. Anhydrous lactose, sprayed dried lactose, crystalline
sorbitol, dicalcium phosphate, dihydrate, granular mannitol, avicel
- When adding ingredients, the ingredients should possess inherit cohesiveness and good
flow properties
- Limitations:
• Stratification-variation in content with differences in size and density
• Drug limited to 30% of tablet weight unless directly compressible
• Interaction between amine drugs and spray-dried lactose
• Development of static charges which prevents uniform distribution
- General steps: (No granulation process)
1. Milling
2. Weighing
3. Mixing
4. Compression
1. Wet granulators
i. Sheer granulators – include a planetary mixer, oscillating granulator (mechanical
process in which the product is pressed through a sieve with a specially shape rotor arm
to obtain a desired particle size), and drying oven
ii. High-speed mixers/granulators
o Diosna/Fielder: stainless steel mixing bowl with a three-bladed main impeller
(Moves or revolves in a horizontal plane or direction) and three-bladed auxiliary
chopper (revolves either vertical or horizontal plane or direction)
o Collete-Gral mixer – based on the bowl and overheard drive of planetary mixer,
but the single paddle is replaces by two mixing shafts (one of the two mixing shafts,
carries the three blades which rotate in the horizontal plane at the base of the bowl;
while the other, carries the smaller blades that acts as a chopper and rotate in the
horizontal plane in the upper regions of the granulating mass)
iii. Fluidized-bed granulators – multi-purpose equipment that includes mixing,
granulation and drying; operates in a bubbling bed regime
iv. Spray-driers – intended for granules made from solution or suspension of drug alone
either in a single excipient or a complete formulation; only used if other methods are not
applicable
v. Sphenoronizers /pelletizer –
o Extrusion/Spheronization – includes a multi-step process in making a uniformly
size spherical shaped granules; end-product: pellets
▪ Main steps:
1. Dry mixing of ingredients to achieve homogenous powder dispersion
2. Wet massing to produce a sufficiently plastic wet mass
3. Extrusion to form rod-shaped particles to form uniform diameter (the
extrude must have enough plasticity to deform but not too much because
the extruded particles will adhere to other particles when collected or
rolled in the sphenorizer
• 3 classes of extruder
a. Screw-feed extruder
b. Gravity-feed extruder
c. Piston-feed extruder
4. Spheronization to round off these rods into spherical particles (Transition
from cylindrical particles with round edges -> dumbbelss -> ellipsoids
-> spherical shape
5. Drying to achieve the desired moisture content
6. Screening to achieve the desired narrow size distribution
▪ Applications:
o Controlled drug release
o Processing – used to increase bulk density, improve flow properties,
and to reduce the problems of dust that are usually encountered in
low density finely divided active and excipient powders
▪ Desirable properties of pellets:
o Uncoated pellets (should maintain these properties)
▪ Uniform spherical shape
▪ Uniform size
▪ Good flow properties
▪ Reproducible packing intro hard gelatin capsules
▪ High strength
▪ Low friability
▪ Low dust
▪ Smooth surface
▪ Ease of coating
o Once coated
▪ It should have a desired drug-release characteristics or
maintain all the properties even they are potent already.
vi. Rotor granulation (Freund granulator) – allows the direct manufacture of sphere
from dry powders
2. Dry granulator
• Two pieces of equipment necessary:
o A machine for compressing the dry powders into compacts or flakes
o A mill for breaking up these intermediate products into granules
- It converts the primary particles into granules using the application of
pressure without the intermediate use of liquid, thus it avoids the heat
temperature combination that may cause the degradation of product
• Sluggers
- large heavy duty rotary press to produce slugs with 25mm in diameter by 10mm-15mm
thick; utilize hammer mill that is suitable for breaking the compacts; used to produce large
tablets
• Roller compaction
- alternative and gentler method compared to sluggers
- the powders mix is being squeezed between two roller to form a compressed sheet (the
sheet produced is normally weak and brittle and breaks immediately into flakes; flakes need
gentler treatment to break them into granules; achieve by screening alone)
- the produced granules are used as a dosage form or subjected into compression or
encapsulation to form a tablet or capsule
D. DRYING
E. FILLING
A. Solids: they are counted by revolving disc, slat counter or breaking a beam of light
- for tablets and capsules
B. Powder or granular products: may be filled by volume using an auger (powder held in a
rotating screw) or a filling cup, or by weight using a bulk feed plus trickle top up
Tablet Manufacturing Techniques:
1. Dry methods - involves direct compression and granulation by compression; and imploys dry
granulation
2. Wet methods – imploys wet granulation
3. Direct compression – usually used in making tablet less than 50mg
Powder compression – reduction in volume of a powder owing to the application of the force
Powder compaction – formation of a porous specimen of a define geometry by powder compression
The process of tableting can be divided into three stages (compaction cycle):
1. Die filling
2. Tablet formation
3. Tablet ejection
• Tablet presses:
- single-punch press AKA. Eccentric press – can make 200 tablets/min
- Rotary press – used in large scale production; can make 10,000 tablets/min
- Parts (rotary press):
o Hopper – where the material is store
o Feed frame – distributes the materials into dies
o Dies – controls the size and shape of tablet
o Punches – compacts material within the dies and controls the shape
o Cams – guides the punches
------------------------------------------------------------------------------------------------------------------------
A. Capping – complete or partial separation of the top or bottom of the body from the main body
B. Lamination – separation of a tablet into a two or more distinct layers
C. Chipping – separation of small portions of the tablet surfaces
Causes:
• Air entrapment among granules – usually air escapes only after pressure is release and during light
granulation; there is air entrapment due to dry granules or powders
Remedy: should have a density fluffy materials, reduce amount of powder and add water or
hygroscopic materials
• Over lubrication
Remedy: validate the amount of lubricants
• Worn and imperfect punches and dies
Remedy: replace the punches and dies
• Carelessness of setting up presses
Remedy: set up the presses correctly to prevent the problem
Tablet processing problems:
D. Picking – removal of materials from the surfaces of the tablets and adherence of the face of the
punch
E. Sticking – adhesion of the granulation to the die or the build-up materials of the punch
Causes:
• Lack of lubricant
Remedy: add lubricant but not too much because it can cause capping, lamination and chipping
• Unpolished surfaces of punches and dies
Remedy: plate the punch faces with chromium to produce a smooth non-adherent face
• Excessive moisture
Remedy: re-dry the granulation
• Soft tablets
Remedy: add more binder or reformulate or dilution of low melting acting ingredients or additives with
high melting materials will also prevent the softening of the granules due to heat and compression and
increase tablet size.
Causes:
Typical batch
8 hours, but easily longer 1.5 hrs – 2 hrs
coating
Functional coating Not usually possible apart from enteric coating Easily adaptable for CRF
• Blistering – causes reduced adhesion between films surface of the tablet due to rapid drying
• Wrinkling – due to improper drying or film former defect
• Bridging – bridging of monogram present in the surface of the tablet core
• Sweating – presence of oily films or droplets of liquid on film surface due to incompatibility of
ingredients
• Orange peel AKA. Roughness –caused by premature drying of atomized droplets of solution or
spraying too viscous solution
• Flaking – due to rapid drying between coats
• Bloom and spotting – due to humid condition or migration of plasticizers to surface coat.
• Compression – makes use of sophisticated tablet compression machine which compresses coating core
shell around the core then has been compressed in another press
• Other new concepts:
1. Pan coating – process used in both sugar and film coating; widely used method
2. Air suspension coating – most dependable method for applying film coats
3. Dip coating – materials to be coated are placed in a basket and dip in a containers of
coating solutions
4. Tablet compression coating – used for special dosage forms, usually for two
incompatible drugs may be separated by placing one in the core and the other in the
coating; can be used for multi-layered compressed tablets
Semi-Solid Preparation
Skin - epidermis - stratum corneum
Dermis
Subcutaneous fat layer
2. Penetration Enhancers
-Facilitate percutaneous absorption by increasing thermodynamic activities of the
penetrant
-It may also increase the degree of hydration or disrupt its lipoprotein matrix.
- decrease resistant to penetrant diffusion
*Conduct additional testing for semi solid preparation if employing penetration
enhancers
3. Stratum Corneum Barrier Efficacy and Dermal Clearance
- to improve absorption; cover or drug can create film
-(in elders they have less hydration) cover with dressing/ drugs that contains films.
-Cutaneous interaction between vasoconstrictor or vasodilators and topically
applied drugs intended for systemic effect may either increased or diminished
bioavailability
-Stratum corneum of elders may offer less resistance to the penetration of
topically applied drugs and delayed dermal clearance
4. Cutaneous Biotransformation
-Epidermis is more metabolically more active than the dermis
-Catabolic enzyme activity is viable in epidermis
- must be physically and chemically stable, doesn’t inhibit or destroy the drug
action
Ointment Bases:
•Oleaginous - (hydrocarbons)
-prepared by vegetable fixed oils and animal fats (lard, olive oil and cottonseed oil)
-Petrolatum
-Petrolatum modified by waxes
-Liquid Pterolatum modified by liquid characteristics
Ex. Liquid petrolatum - petrolatum + polyethylene - gel-like consistency
-Petrolatum USP: tasteless, odorless, unctuous material with melting range of
38 to 60 degC
-Color ranges from amber to white (white petrolatum, white ointment, yellow
ointment )
-antioxidants and preservatives
Property: effective as occlusive dressing, increase hydration effect, renders
emollient effect
•Preparation:
*Incorporation- small quantity 30-90g
*Includes levigation -use mineral oil or PEG
*Fusion (emulsion formulation)
1. combining of all soluble components
2. Heating to 75celcius
3. Add water soluble ingredients to oil soluble ingredients for 75 degrees
celcius in a separated container
-Constant agitation,
-Congealed means emulsion has formed, then mixture is cooled, once
achieve add medicinal ingredients
-Adding volatile oils or aromatic materials cooled to 35 degree celcius
B. Creams
•O/W type; shaving creams, hand creams, foundation creams
• W/O type, Vanishing creams, cold cream, emollient cream
-Vanishing creams: o/w containing large % of water & stearic acids
C. Gels
-Dispersion of small/large molecules in an aq. vehicle which has gel like
consistency
Gelling agent:
Synthetic macromolecules= carbomers 934
cellulose derivatives= carboxylmethylcellulose (CMC),
hydroxypropylmethylcellulose (HPMC)
and natural gums= tragacanth
Types:
•Single Phase gels - macromolceules are uniformly distributed throughout the
liquid.
•Two phase Systems/Magma: relatively large, much distinct particles
compared to single phase
Problems/terms related:
•Imbibition- taking up liquid without measurable increase in volume
•Syneresis - gel sinks because of loss of liquid
•Swelling - taking up of liquid, increase of volume
•Thixotropy- reversible gel-sol formation w/out volume of temperature
changes
Semi-solid Preparation
Other Preparation:
Dressing- - resemble ointment, protection for burns, gauze, remain semi solid
at body temp, liquefy at 50 degrees
•Petroleum gauze- sterile dressing adding sterile molten prepared by a precut
sterile gauze: 60g petrolatum & 20g gauze
Pastes- gelling agent = carboxymethylcellulose - single phase aqueous gel
-Thicker, stiffer , can absorb more serous charges
-Disadvantage: Poor occlusive property , applied at moist lesions
-Need to use mineral oil or veegetable oil to remove the paste
-Fatty paste - zinc oxide paste
-Single-phase aqueous gel- CMC sodium Paste
-Fatty paste and single-phase aqueous gel
Ex. Zinc oxide paste, Carboxymethylcellulose Sodium Paste and
Triamcinolone Acetonide Dental Paste
Plasters - semi solid/solid adhesive masses spread on backing of paper, fabric,
mole skin, or plastic adhesive
-Advantage: provides a clean skin surface when removed, intended
for protection and support and furnish and occlusive, maceration action
to bring a medication to close contact with the skin.
E. Suppositories and inserts -most useful with pedia and geriatrics patient
-Contains stiffening agents
-Sodium stearate(glycerin suppositories) - stiffening agent
Types:
•Vaginal- AKA”pessaries”, cone in shape, globular, oviform
5g, 70mm
-base: glycerinated gelatin
Bases:
•Fatty/Oleaginous
Ex. Cocoa butter, fattibase and wecobee base
•Water-soluble and water-miscible
Ex. Polyethylene glycol and Glycerinated gelatin
•Miscellaneous base
Ex. Polyoxyl -40 stearate
Preparation:
•Rolling- AKA “hand shape suppositories” (with skill and expertise required)
-Simpliest and oldest method
-Avoid complication of heating and molding
Packaging:
•Tightly closed glass containers - glycerin or glycerinated gelatin supps are
usually
•Compartmented boxes- supps are usually held in this type of container.
•Opaque material (metallic foil or PVC polyethylene)- commercial supps
•Continuous strip
•Slide boxes
•Plastic boxes
-Cocoa butter and low melting point supps are stored in a refrigerator.
-Water soluble/miscible- not stored in ref because it doesn’t melt in body temp
only in body fluids.
Mixing of semi-solids:
-Mixing using mechanical mixers- drug substances that are finely divided form
added slowly/ sifted into vehicle contained in a mixer.
1. Planetary mixers
-Mixing blade is set-off center and is carried on a rotating arm
-Has double rotation similar to spinning planets rotating around sun.
2. Sigma blade mixer
-Depends action on the close intermeshing of the two blades
- blades resemble greek letter E in shape
-For paste and ointments.